Progress in Development of Herpes Simplex Virus Gene Vectors for Treatment of Rheumatoid Arthritis

Arthritis is presently incurable and poorly treatable, but there are good grounds for expecting gene therapy to improve matters considerably. Although local ex vivo delivery of anti-arthritic genes to the synovial lining of joints has shown considerable promise, intraarticular gene delivery may be desirable. Herpes simplex virus (HSV) may be a viable vector for in vivo transfer of anti-arthritic genes to joints. HSV has the advantages of high infectivity, large carrying capacity and high titer. The large packaging capacity would permit the inclusion of multiple anti-arthritic genes and necessary regulatory elements. Recombinant vectors produced by this laboratory infect synovial cells efficiently, permitting prolonged expression of transgenes in vitro and in vivo without evidence of cytotoxicity. Further improvements to this vector system include taking advantage of an endogenous HSV 'stealthing' gene, ICP47, which interferes with formation of antigen-class I complexes. Inclusion of inducible promoters to appropriately regulate expression of anti-arthritic genes should further improve this system.